Malaria Vaccine Development Branch (MVDB) General Description: The Malaria Vaccine Development Unit (MVDU) is an NIAID initiative working in close collaboration with DMID to respond to the global need for vaccines against malaria. We now have produced six cGMP recombinant protein products: AMA1-FVO, AMA1- 3D7, MSP1(42)-FVO, MSP1(42)-3D7, Pfs25, Pvs25. Three of these antigens (Pvs25H, AMA1-FVO and AMA1-3D7) are in three different Phase 1 clinical trials. The Pvs25H trial has been completed; the AMA-FVO and AMA1-3D7 proteins have been combined as a mixture,designated AMA1-C1, which is currently being tested in two Phase 1 field trials, one in adults in the US and one in adults in Mali. We are also collaborating on the Phase I field testing in Mali of another malaria vaccine, FMP1. We have completed the IND application for clinical testing of two more malaria blood-stage antigens, MSP1(42)-FVO, and MSP1(42)-3D7, and this Phase 1 U.S. trial is in progress. We are also in the process of completing two additional INDs, one including both Pvs25 and Pfs25, as well as an IND application for the further clinical testing of AMA1-C1 with the addition of oligo-DNAs designed to enhance immunogenicity. This technology takes advantage of the capacity of oligo-DNAs to stimulate receptors of the innate immune system which in turn enhance specific adaptive immune response. Moreover, if successful, it is a platform technology which can be applied to other vaccine candidates. Several other antigens for both asexual and mosquito stages are in the predevelopment phase. In the past year we have made considerable progress in developing the assays (e.g., in vitro growth inhibition assays) required to evaluate the outcome of malaria vaccine trials. With our colleages from the University of Mali, we have established a field vaccine testing capability and have obtained the baseline epidemiologic information required to prepare protocols for future Phase 2 trials in the field.